The techniques of cell and molecular biology are being used to analyze mechanisms which control the expression of differentiated genes in normal and leukemic hematopoietic cells and regulate their differentiation and proliferation. Mutant erythroleukemia (MEL) cells will be fused with human erythroid and non-erythroid cells to generate hybrid cells containing human globin genes. The state of the human and mouse globin genes in these hybrid cells and the MEL parent cell will be studied during induction of gene transcription by testing the sensitivity of these genes to nuclease (DNase II) digestion during the induction process. Such hybrid cells containing human globin genes will also be used to determine if genetic elements controlling the expression of globin genes are on the same or different chromosomes as are the structural genes. Constitutive and inducible markers of myeloid, lymphoid, and erythroid hematopoietic cells will be studied in hybrids derived by fusion of leukemic cells exhibiting erythroid, myeloid and lymphoid phenotypes. The sensitivity of these hybrid cells to erythropoietin or colony-stimulating-factor will also be tested to analyze the genetic determinants which control proliferation of these cells. BIBLIOGRAPHIC REFERENCES: Anderson, W.F., Deisseroth, A.B., Velez, R., Nienhuis, A.W., Ruddle, F.H., and Kucherlapati, R.S.: A New Technique for Mapping Hemoglobin Genes. Human Gene Mapping 3, Vol. XII, No. 7: 367-371, 1976. Deisseroth, A.,: Cell fusion. In Evans, V. (Ed.): Tissue Culture Association Manual. Rockville, Md., Tissue Culture Association, 1976, pp. 256-259.